Both UVR induced immunosuppression and genetic damage are known to contribute to skin cancer in humans and experimental animals. Failure of the skin immune system to respond after UVR exposure to preneoplastic cells bearing neoantigens may contribute significantly to the development of skin cancer. UVR induced suppression of delayed-type hypersensitivity (DTH) is functionally similar and may be used as a marker to determine individual susceptibility to UV-induced immunosuppression as a risk factor for the induction of skin cancer in humans and selected mouse strains. In addition, UVR induced DNA damage and individual DNA repair efficiencies may also contribute to host susceptibility for skin cancer. Recent evidence indicates that tumor necrosis factor alpha (TNFalpha) may mediate UVR induced immune suppression of DTH in humans and in selected strains of mice. Genetic polymorphisms at the TNFalpha locus (intron 1 BamHI RFLP and a 5